Biomedical subjects

R Lu

Publications and source records attributed to R Lu.

At least 91 records · Page 5Linked to original sources

PubMed1998

[Three dimensional reconstruction of human permanent teeth].

OBJECTIVE: Dental anatomy is one of the most important basic courses in the education of stomatology. The deep understanding of morphologic characters is closely instructive to the clinic of endodontics, oral surgery, orthodontics and prosthodontics. METHODS: In present study, 32 permanent teeth from a skull specimen were inputted into computer after the processes of burying, grinding, photographing, scanning and recognizing. By the techniques of reconstruction, the 3D stereo tooth models were retrieved from 2D digital data. RESULTS: On the basis of those 3D data, computer graphics techniques were used to realize the lighted, smoothed and shaded teeth. CONCLUSION: Such a series of data teeth might be applicated as a corner stone of the computer aided instruction (CAI) in stomatology.

Computer-Assisted Instruction↗

PubMed1998

[Fate of massive retrieved human bone allografts].

OBJECTIVES: To study retrieved massive human allograft specimen after they had been in situ for four to sixty-five months, and to investigate the changes union, bone replacement and degradation of articular cartilage. METHOD: BMP gene expression in the specimen was also studied with in situ hybridization, immunohistochemical methods, and the observations were correlated with the clinical and isotope scan date. RESULT: The union between the allograft and the host was achieved by the formation of an external callus derived from the cortex of the host. New bone replacement took place slowly. Analysis of the articular cartilage revealed evidence that some chondrocytes had survived in non bearing area of the articular. The expression of BMP in the surface of the cortex and united callus was positive 4 months after implantation. But it was negative in the center of cortex after it had been implanted for over 12 months. An external callus formed from the cortex of the host. Some chondrocytes survived in non-bearing area of the articular. Neovasculature penetrated into osteoarticular. CONCLUSION: Bone absorption may be the cause of collapse of articular surface. The results suggest that large allografts in humans are osteo-conductive rather than inductive. Incomplete repair of osteon may be related to slowed replacement of massive human allograft.

Adolescent↗

PubMed1998

[Pathophysiology and surgical treatment on Relaxed Pelvic Floor Syndrome].

OBJECTIVE: To study the pathophysiology of the "Relaxed Pelvic Floor Syndrome (RPFS)" and to assess the value of the "Pelvic Cavity Fixation Operation (PCFO)" for the syndrome. METHOD: 11 patients, who were diagnosed as having RPFS, underwent standardized PCFO. All the patients were followed for a mean time of 19 months (5 - 72 months). RESULT: The main syndromes and signs included difficulty in defecation, inability to empty the rectum properly, fullness of perineum, protrusion of perineum at bearing down, back-inclining uterus, relaxation of the rectum on digital examination. The anorectal dynamics showed that the sequence pressure and rest pressure of the anal cannel were lower and the time of contraction of the anal cannel decreased than that of the normal controls. The rectum sensation was damaged slightly. Defeacography showed that there were relaxing changes in several systems in the pelvic cavity. Operatively, it was easy to see the relaxation of the supporting structure of the colon, rectum, uterus and the lower position of the peritoneal cavity. PCFO has achieved good results. Seven patients were free of symptoms completely and 4 improved. CONCLUSION: The relaxing changes of the supporting tissue of many viscus fefer to several systems are the pathophysiologic of the RPFS. "Pelvic Cavity Fixation Operation" is useful in the treatment of the syndrome.

Adult↗

PubMed1998

[Immunohistochemical investigations of congenital pseudarthrosis of the tibia].

OBJECTIVE: To investigate the etiology and pathology of congenital pseudarthrosis. METHOD: Sixty-three specimens were taken from 21 CPT patients. The antibodies, which were used for immunohistochemical studies, were produced against (1) NF-200 or S-100 protein; (2) type I or III collagen; (3) PCNA. The control specimens were taken from neurofibromatosis and traumatic pseudarthrosis. SABC staining was performed. RESULT: Low positive expression of NF-200 (3.2%) and S-100 (4.8%) was noted in the CPT lesion, whereas high expression of NF-200 (85.2%) and S-100 (88.9%) in the lesion of neurofibromatosis. The soft tissues in CPT had a higher ratio of type III to I collagens in comparison with traumatic pseudarthrosis. Positive expression of PCNA (95.2%) was significantly higher in the soft tissues than that (2.5%) in traumatic pseudarthrosis. CONCLUSION: CPT is a disease of non-neuro origin. Its occurrence has no direct relation with neurofibromatosis. CPT has its characteristic pathology in the periosteum rather than in the bone. The pathological fracture or non-union of CPT is caused by fibromatosis, which has a strong activity of cellular proliferation and corrosion. CPT has its pathological property similar to a tumor.

Adolescent↗

PubMed1998

[The osteoinductivity and the dose-effect relationship with implantation of reconstituted bone xenograft: experimental study].

OBJECTIVE: To observe osteoinductivity and the dose-effect relationship with administration of reconstituted bone xenograft (RBX). METHOD: A posterior thigh muscle pouch model with RBX transplantation was established in BALB/C mice. Samples were treated at regular postoperative intervals for radiologic, histomorphologic and ALP examinations. RESULT: (1) In the groups that had been implanted with RBX, the osteoinductivity was positively correlated with the bBMP contents in RBX (r = 0.7204, P < 0.01), showing a dose-dependent relationship; (2) satisfactory osteogenesis was noted in the RBX I group, whereas no substantial bone formation was seen in the group implanted with bBMP alone apart from some evidence of osteogenic effect; (3) the alkaline phosphatase activity attained its peak on the 7th day postoperatively and kept still higher to the 42nd day. CONCLUSION: RBX is a highly osteoinductive grafting material with the treated homologous cancellous bone being a good slow-delivery carrier which can enhance the osteoinductive capacity of bBMP.

Alkaline Phosphatase↗

PubMed1998

Characterization of cembranoid interaction with the nicotinic acetylcholine receptor.

The class of diterpenoids with a 14-carbon cembrane ring, the cembranoids, includes both competitive and noncompetitive inhibitors of the nicotinic acetylcholine receptor (AChR). All 20 coelenterate-derived cembranoids studied in this report inhibited [piperidyl-3,4-3H]-phencyclidine ([3H]-PCP) binding to its high-affinity site on the electric organ AChR, with IC50s ranging from 0.9 microM for methylpseudoplexaurate to 372 microM for lophotoxin. Inhibition was complete with all cembranoids but lophotoxin and most Hill coefficients were close to 1. Methylpseudoplexaurate and [3H]-PCP binding was competitive. Methylpseudoplexaurate and the fourth most potent cembranoid, eunicin, competed with each other for [3H]-PCP displacement, indicating that there exist one or more cembranoid sites on the AChR. Cembranoid affinity for the AChR correlated with hydrophobicity, but was also dependent on other features. Methylpseudoplexaurate and n-octanol also competed with each other for [3H]-PCP displacement, indicating that the cembranoid site is linked to the n-octanol site on the AChR. Unlike lophotoxin, the five cembranoids tested did not inhibit [125I]Tyr54-alpha-bungarotoxin binding to the AChR agonist sites. All seven cembranoids tested on oocyte-expressed electric organ AChR reversibly blocked acetylcholine-induced currents, although the inhibitor concentration curves were shallow and the inhibition was incomplete.

Acetylcholine↗

PubMed1997

Tissue-specific expression of herpes simplex virus thymidine kinase gene delivered by adeno-associated virus inhibits the growth of human hepatocellular carcinoma in athymic mice.

About 70% of hepatocellular carcinomas are known to express alpha-fetoprotein, which is normally expressed in fetal but not in adult livers. To induce herpes simplex virus-thymidine kinase expression in these cancer cells, we constructed an adeno-associated viral vector containing the HSV-TK gene under the control of the alpha-fetoprotein enhancer and albumin promoter. We previously demonstrated in vitro that although this vector can transduce a variety of human cells, only transduced AFP and albumin-expressing hepatocellular carcinoma cell lines were sensitive to killing by ganciclovir (GCV). In the present study, we explored the effect of this vector on hepatocellular carcinoma cells in vivo. Subcutaneous tumors generated in nude mice by implanting hepatocellular carcinoma cells previously transduced with this vector shrank dramatically after treatment with GCV. Bystander effect was also observed on the tumors generated by mixing transduced and untransduced cells. To test whether the tumor cells can be transduced by the virus in vivo, we injected the recombinant adeno-associated virus into tumors generated by untransduced hepatocarcinoma cell line. Tumor growth were retarded after treatment with GCV. These experiments demonstrate the feasibility of in vivo transduction of tumor cell with rAAV.

Animals↗

PubMed1997

Failure of a second X-ray dose to activate nuclear factor kappaB in normal rat astrocytes.

Induced gene expression and subsequent cytokine production have been implicated in the normal tissue injury response to radiotherapy. However, studies of radiation-induced gene expression have used single radiation doses rather than the fractionated exposures typical of the clinical situation. To study the effects of multiple radiation doses on gene expression, we investigated nuclear factor kappaB (NFkappaB) DNA binding activity in primary astrocyte cultures after one and two exposures to x-rays. After a single dose of x-rays (3.8-15 gray (Gy)), NFkappaB binding activity in astrocytes increased in a dose-dependent manner, reaching a maximum by 2-4 h and returning to control levels by 8 h after irradiation. In split-dose experiments, when an interval of 24 h was used between two doses of 7.5 Gy, the second 7.5-Gy exposure failed to induce NFkappaB activation. The period of desensitization induced by the first radiation exposure was dose-dependent, persisting approximately 72 h after 7.5 Gy compared with 24 h after 1.5 Gy. No changes in IkappaBalpha protein levels were detected. However, the presence of a transcription inhibitor prevented the desensitizing effect of the initial irradiation. Irradiation also prevented NFkappaB activation in astrocytes by a subsequent exposure to H2O2, but it had no effect on the activation induced by tumor necrosis factor-alpha. These data indicate that an initial x-ray exposure can desensitize astrocytes to the NFkappaB-activating effects of a subsequent radiation exposure. Furthermore, they suggest that this desensitization depends on gene transcription and may have some specificity for NFkappaB activation mediated by reactive oxygen species.

Animals↗

PubMed1997

Determination of Association Constants for Cyclodextrin-Surfactant Inclusion Complexes: A Numerical Method Based on Surface Tension Measurements

Inclusion complexes of beta-cyclodextrin (beta-CD) with sodium octyl sulfonate (C8As), sodium dodecyl sulfonate (C12As), and sodium hexadecyl sulfonate (C16As) in aqueous solutions are studied by surface tension measurement at the air/water interface at different temperatures. At fixed concentrations of the surfactants, the surface tension increases with an increase in beta-CD concentration to a maximum value, at which it holds. The surface tension curves of the surfactants in the presence of beta-CD are higher than those in the absence of beta-CD. The curves rise higher with the increase in beta-CD concentration for each surfactant. The apparent critical micelle concentrations (CMC*) of the surfactants vary linearly with beta-CD concentration. The CMC* and surface tension values (including those after the CMC*) for the same system decrease with increase in temperature. A numerical method based on surface tension measurements is developed to determine the association constants for 1:1 inclusion complexes. This method is very reliable and easy to perform. The results demonstrate that the longer the hydrophobic tail of the surfactant, the greater the association constant with beta-CD, and that for the same surfactant the association constant is higher at lower temperatures.

Journal Article↗

PubMed1997

A mammalian DNA repair enzyme that excises oxidatively damaged guanines maps to a locus frequently lost in lung cancer.

BACKGROUND: Guanine residues in the genome are vulnerable to attack by free radicals and reactive oxygen species. A major lesion thus produced, 8-oxoguanine (OG), causes mutations by mis-pairing with adenine during replication. In bacteria and budding yeast, OG is removed from the genome through the action of base-excision DNA repair (BER) enzymes, which catalyze expulsion of the aberrant base and excision of its sugar moiety from the DNA backbone. Although OG is known to be produced in and cleansed from mammalian genomes, the enzymes responsible for OG repair in these cells have remained elusive. RESULTS: Here, we report the cloning and biochemical characterization of mammalian BER enzymes that specifically target OG residues in DNA. These 8-oxoguanine DNA glycosylases, hOgg1 (human) and mOgg1 (murine), are homologous to each other and to yeast Ogg1. They also contain an active site motif - the Helix-hairpin-Helix, Gly/Pro-rich-Asp motif - characteristic of a superfamily of BER proteins with a similar core fold and active site geometry. Both hOgg1 and mOgg1 exhibit exquisite selectivity for the base opposite OG in DNA, operating with high efficiency only on OG base-paired to cytosine. Furthermore, hOgg1 and mOgg1 are unable to process a panel of alternative lesions, including 8-oxoadenine, yet bind with high affinity to synthetic abasic site analogs. The proteins operate through a classical glycosylase/lyase catalytic mechanism; mutation of a catalytically essential lysine residue results in loss of catalytic potency but retention of binding to OG-containing oligonucleotides. The hOGG1 gene is localized on the short arm of chromosome 3 (3p25/26) in a region commonly deleted in cancers. CONCLUSIONS: These results conclusively establish the existence and identity of an 8-oxoguanine DNA glycosylase/lyase in human and murine cells, completing the triad of proteins that together protect mammals from the genotoxic effects of guanine oxidation. The observation that at least one allele of hOGG1 is commonly deleted in cancer cells suggests that such cells may possess a reduced capacity to counter the mutagenic effects of reactive oxygen species, a deficiency that could increase their overall genomic instability. This speculation is fueled by recent observations that cells constitutively active for the Ras/Raf pathway constitutively produce high levels of superoxide, a known generator of OG.

Amino Acid Sequence↗

PubMed1997

Early onset of reproductive function in normal female mice treated with leptin.

Numerous studies have revealed an association between nutritional status, adiposity, and reproductive maturity. The role of leptin, a hormone secreted from adipose tissue, in the onset of reproductive function was investigated. Normal prepubertal female mice injected with leptin grew at a slower rate than controls as a result of the hormone's thinning effects, but they reproduced up to 9 days earlier than controls and showed earlier maturation of the reproductive tract. These results suggest that leptin acts as a signal triggering puberty, thus supporting the hypothesis that fat accumulation enhances maturation of the reproductive tract.

Animals↗

PubMed1997

Protection by capsaicin against attenuated endothelium-dependent vasorelaxation due to lysophosphatidylcholine.

Previous studies have shown that pretreatment with calcitonin gene-related peptide (CGRP), a principal transmitter in sensory nerves, can protect the endothelial cell. We therefore evaluated whether in vivo capsaicin treatment prevents endothelial damage elicited by lysophosphatidylcholine (LPC) in the rat aorta. Acute treatment or repeated pretreatment with capsaicin resulted in stimulation of neurotransmitter release from sensory nerves or depletion of their transmitter content respectively. Vasodilator responses to acetylcholine (ACh) were examined in the aorta of these animals. Acute application of capsaicin (50 mg/kg) increased the plasma concentration of CGRP-like immunoreactivity (CGRP-LI) concomitantly with a reversal of the inhibition by LPC of endothelium-dependent ACh-induced relaxation in the isolated rat aorta. After repeated pretreatment with capsaicin to deplete sensory nerve neurotransmitter content the effects of capsaicin were absent as shown by the plasma CGRP-LI concentration and the vasodilator response to ACh. The results demonstrate that systemic capsaicin treatment, which evokes the release of CGRP from sensory nerves, protects the endothelial cell. The present study also suggests that CGRP may be an endogenous vascular protective substance.

Acetylcholine↗

PubMed1997

The prostaglandin transporter is widely expressed in ocular tissues.

Prostaglandins (PGs) play important physiological and therapeutic roles in the eye. Our laboratory recently identified a novel PG transporter in the rat that we call "PGT" (Science 268:866, 1995). We have also recently cloned the human PGT cDNA (J Clin Invest 98:1142, 1996). To determine whether PGT might play a role in human ocular tissues, we performed Northern blot analysis of RNA obtained from human ocular tissues and from the nonpigmented ciliary epithelium cell line "ODM-2." PGT transcripts were clearly evident in all ocular tissues. Given that the functional profile of PGT expressed in vitro strongly suggests a role in PG uptake and degradation, the present results suggest that PGT may function in various regions of the human eye for purposes of terminating the signal(s) produced by locally-synthesized PGs.

Adult↗

PubMed1997

The critical active-site amine of the human 8-oxoguanine DNA glycosylase, hOgg1: direct identification, ablation and chemical reconstitution.

BACKGROUND: Base-excision DNA repair (BER) is the principal pathway responsible for the removal of aberrant, genotoxic bases from the genome and restoration of the original sequence. Key components of the BER pathway are DNA glycosylases, enzymes that recognize aberrant bases in the genome and catalyze their expulsion. One major class of such enzymes, glycosylase/lyases, also catalyze scission of the DNA backbone following base expulsion. Recent studies indicate that the glycosylase and lyase functions of these enzymes are mechanistically unified through a common amine-bearing residue on the enzyme, which acts as both the electrophile that displaces the aberrant base and an electron sink that facilitates DNA strand scission through imine (Schiff base)/conjugate elimination chemistry. The identity of this critical amine-bearing residue has not been rigorously established for any member of a superfamily of BER glycosylase/lyases. RESULTS: Here, we report the identification of the active-site amine of the human 8-oxoguanine DNA glycosylase (hOgg1), a human BER superfamily protein that repairs the mutagenic 8-oxoguanine lesion in DNA. We employed Edman sequencing of an active-site peptide irreversibly linked to substrate DNA to identify directly the active-site amine of hOgg1 as the epsilon-NH2 group of Lys249. In addition, we observed that the repair-inactive but recognition-competent Cys249 mutant (Lys249-->Cys) of hOgg1 can be functionally rescued by alkylation with 2-bromoethylamine, which functionally replaces the lysine residue by generating a gamma-thia-lysine. CONCLUSIONS: This study provides the first direct identification of the active-site amine for any DNA glycosylase/lyase belonging to the BER superfamily, members of which are characterized by the presence of a helix-hairpin-helix-Gly/Pro-Asp active-site motif. The critical lysine residue identified here is conserved in all members of the BER superfamily that exhibit robust glycosylase/lyase activity. The ability to trigger the catalytic activity of the Lys249-->Cys mutant of hOgg1 by treatment with the chemical inducer 2-bromoethylamine may permit snapshots to be taken of the enzyme acting on its substrate and could represent a novel strategy for conditional activation of catalysis by hOgg1 in cells.

Amines↗

PubMed1997

Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor.

The human host cell factor (HCF) is expressed in a variety of adult and fetal tissues, and its gene is conserved in animals as diverse as mammals and insects. However, its only known function is to stabilize the herpes simplex virus virion transactivator VP16 in a complex with the cellular POU domain protein Oct-1 and cis-acting regulatory elements in promoters of immediate-early viral genes. To identify a cellular function for HCF, we used the yeast two-hybrid system to identify a cellular ligand for HCF. This protein, Luman, appears to be a cyclic AMP response element (CRE)-binding protein/activating transcription factor 1 protein of the basic leucine zipper superfamily. It binds CREs in vitro and activates CRE-containing promoters when transfected into COS7 cells. This activation of transcription was synergistically enhanced by the presence of CCAAT/enhancer-binding protein elements and inhibited by AP-1 elements in the promoter. In addition to a basic DNA binding domain, Luman possesses an unusually long leucine zipper and an acidic amino-terminal activation domain. These features in Luman are also present in what appear to be homologs in the mouse, Drosophila melanogaster, and Caenorhabditis elegans. Luman and VP16 appear to have similar mechanisms for binding HCF, as in vitro each competitively inhibited the binding of the other to HCF. In transfected cells, however, while VP16 strongly inhibited the ability of GAL-Luman to activate transcription from a GAL4 upstream activation sequence-containing promoter, Luman was unable to inhibit the activity of GAL-VP16. Luman appears to be a ubiquitous transcription factor, and its mRNA was detected in all human adult and fetal tissues examined. The possible role of HCF in regulating the function of this ubiquitous transcription factor is discussed.

Adult↗

PubMed1997

Leptin treatment rescues the sterility of genetically obese ob/ob males.

Leptin, a hormone secreted from white adipose tissue, has been shown to normalize the body weight of ob/ob but not db/db mice as postulated by Coleman in his classical parabiosis experiments. The major effect of leptin is therefore to decrease food intake, thus resulting in a breakdown of fat stores. Recently, we have suggested that leptin plays a role in reproductive physiology based on the observation that leptin treatment but not food restriction rescues the sterility of ob/ob females. In the present communication, we treated sterile ob/ob males with leptin and asked whether fertility could be induced, thus selecting their reproductive ability as the endpoint of the experiment. Our results show that all food-restricted ob/ob males are unable to impregnate normal C57BL/6J females. However, all leptin-treated ob/ob males fertilized normal females mice that carried out normal pregnancies and deliveries, demonstrating that the reproductive capacity of ob/ob males was corrected only with leptin treatment. Furthermore, reproductive indices such as testicular weight and histology are normalized in leptin-treated animals. Therefore, as in ob/ob females, leptin plays a significant role in the male mouse reproductive pathways.

Animals↗

PubMed1997

Elevation of an endogenous inhibitor of nitric oxide synthase in diabetic rat serum.

AIM: To study the endogenous inhibitor of NO synthase NG,NG-dimethyl-arginine (DMA) in the diabetic rat serum. METHODS: In streptozocin-induced diabetic rats, the serum DMA level and endothelium-dependent vasorelaxation to acetylcholine (ACh) were determined. RESULTS: The serum DMA concentration was increased in the diabetic rats compared with their age-matched controls (5.4 +/- 1.0 vs 0.7 +/- 0.3 mumol.L-1, P < 0.01). The serum malondialdehyde (MDA) level was also increased in the diabetic rats compared with controls (2.5 +/- 0.3 vs 1.5 +/- 0.1 mumol.L-1, P < 0.01). Vasodilator response to ACh was impaired in diabetic thoracic aortas, which was improved by preincubation with L-arginine 1 mmol.L-1. CONCLUSION: Hyperglycemia elevated the endogenous DMA content, which contributed to attenuated endothelium-dependent vasorelaxation in streptozocin-induced diabetic rats.

Animals↗

PubMed1997

Effect of calcitonin gene-related peptide-induced preconditioning on attenuated endothelium-dependent vasorelaxation induced by lysophosphatidylcholine.

AIM: To study the effects of calcitonin gene-related peptide (CGRP)-induced preconditioning on the inhibition of endothelium-dependent vasorelaxation to acetylcholine (ACh) by lysophosphatidylcholine (Lys) in the isolated rabbit and rat thoracic aortas. METHODS: Endothelium-dependent relaxation to ACh was studied in the aortic rings precontracted with phenylephrine 0.1 mumol.L-1 in the absence or presence of Lys. RESULTS: On the rabbit aortic rings, Lys 5 mg.L-1 impaired vasodilator responses to ACh. Pretreatment with CGRP 0.1 mumol.L-1 for 5 min attenuated the inhibition of vasodilator responses to ACh by Lys. The effect of CGRP was blocked by 1-(5-isoquinolinysulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C (PKC) (% relaxations to ACh 1 mumol.L-1 were 88 +/- 4, 28 +/- 10, 65 +/- 13, and 25 +/- 10 for control, Lys, Lys + CGRP, and Lys + CGRP + H-7, respectively). The same effects of CGRP were shown in the rat aortic rings, and the effect of CGRP was also abolished by H-7 (% relaxations to ACh 1 mumol.L-1 was 84 +/- 10, 55 +/- 11, 76 +/- 11, and 50 +/- 14 for control, Lys, Lys + CGRP, and Lys + CGRP + H-7, respectively). CONCLUSION: CGRP-induced preconditioning protected the endothelium against injury elicited by Lys, the effect of CGRP is related to the activation of PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗